There has been a recent expansion in the distribution and the incidence of leishmaniasis. Visceral leishmaniasis is particularly troublesome as it causes most fatalities. India, Nepal, Bangladesh, Sudan and Brazil harbor 90% of the worldwide reported VL cases. Amongst the millions at risk in India, the state of Bihar accounts for nearly 90% of cases, followed by the states of West Bengal, Jharkhand and Eastern Uttar Pradesh. This proposed Tropical Medicine Research Center is divided into 3 projects that will address epidemiological, clinical, immunological and genetic factors that influence the prevalence, distribution and pathogenesis of visceral leishmaniasis in individuals and communities in Bihar State in India. The individual projects that make up this TMRC are also designed to provide new data that will be more broadly applicable to the continuing development of control programs in the other major global foci of disease, including development of novel vaccines and diagnostic aids. Themes of the three major projects are: Project 1: Clinical and epidemiological studies of Visceral Leishmaniasis in Bihar, India: Goals of this project are to provide the epidemiological and clinical evidence that is required to guide efforts to eliminate or control visceral leishmaniasis in the state of Bihar, India, and to provide epidemiological data that will more broadly inform future control programs including development of novel vaccines and diagnostic aids. Project 2: The role of regulatory T cell subsets and cytokines in the pathogenesis of human VL in Bihar, India. This project is a focused study that will investigate the role of regulatory T cells and suppressive cytokines in the pathogenesis of human visceral leishmaniasis, with a view toward the development of immune-based therapies that will reverse the immunosuppression associated with active disease. Project 3: Genetic risk factors for Visceral Leishmaniasis in Bihar, India. This project will address genetic factors that underly genetic susceptibility to visceral leishmaniasis, with the purpose of identifying genes/ mechanisms/ pathways that contribute to the pathogenesis of disease. The TMRC will bring together a unique combination of epidemiologists, clinicians, immunologists and molecular geneticists to tackle the problem of visceral leishmaniasis in one of the major global foci of this fatal disease.